Curtis Chong, center, with
advisers David Sullivan and Jun Liu. An MD/PhD candidate in
pharmacology and molecular sciences, Chong has already
identified potential new uses for three FDA-approved
drugs.Photo by Will Kirk / HIPS

School of Medicine recognizes the talents of students and
fellows

By Audrey HuangJohns Hopkins Medicine

How we listen to ourselves when we talk, the
underlying defect in a rare neurological disorder and a
plan for identifying potential drugs faster and cheaper are
a few of many research projects that will be honored this
year at the 30th annual Young Investigators' Day at Johns
Hopkins. Eleven students and seven fellows will be
celebrated, along with all young investigators in the
School of Medicine.

"The trainees at Hopkins are the driving force behind
our research here," said Chi V. Dang, vice dean for
research in the School of Medicine. "We would be nowhere
without them."

The Young Investigators' Day program will start at 4
p.m. on Thursday, April 19, in the School of Medicine's
Mountcastle Auditorium, East Baltimore campus, where
selected awardees will present their research and all will
receive honors. A poster session and reception will follow.

"This really is a celebration of all of our students
and fellows," said Randall Reed, a professor of molecular biology and
genetics and chair of the selection committee.
"Selecting the awardees is one of the most difficult tasks
that the committee members face each year. The applicants
all were outstanding."

Renee Domergue, a PhD candidate in the Cellular
and Molecular Medicine Program, is the recipient of the
Alicia Showalter Reynolds Award. "I've been attending Young
Investigators' Day celebrations since I started at Hopkins
and always have been impressed with the caliber of work,"
she said. "It's a tremendous honor to be considered in the
same league as the other recipients past and present."

Domergue's research in Brendan Cormack's lab
discovered that the culprit behind yeast infections adapts
to hosts by sensing and adjusting to available nutrients it
needs to survive.

Young Kwon, a PhD candidate in biological
chemistry and recipient of one of four Paul Erlich
Research Awards, said, "I am so honored to be recognized by
this award. When I was a second-year student, a senior
student in our lab received a Young Investigators' Award,
and witnessing that inspired and encouraged me to be as
successful."

While working with mentor Craig Montell, Kwon
discovered that a fruit fly gene called Lazaro is required
for a second biochemical pathway that controls the activity
of a protein called the TRP channel, found in fruit fly
neurons and responsible for sensing light. The fly TRP
channel is the founding member of a family of related
proteins in mammals that are essential for guiding certain
nerves during development and for responding to stimuli
including heat, taste and sound.

Also recognized for research relating to how we
perceive light was another Paul Erlich awardee,
postdoctoral fellow Hsi-Wen "Rock" Liao, who while
working in King-Wai Yau's lab discovered a new pigment
called melanopsin in the light-sensing cells of the retina.

Seyun Kim, a PhD candidate in biological
chemistry, praises his thesis adviser, Pierre Coulombe,
"who is always inspirational, creative, encouraging and
supportive. Without Pierre I wouldn't have anything
fruitful." Kim, who received the Martin and Carol Macht
Award, discovered that a protein long thought to provide
only mechanical support for keeping cells and tissues from
literally falling apart turns out to have much wider
utility. The protein, K17, also influences wound healing
and maintains the structural integrity of hair follicles.
Kim's work, published in Nature last year, may have
implications for preventing or treating chronic wounds such
as pressure or bedsores arising from long periods of
immobility.

Medical student Kaisorn Chaichana, who received
a Paul Erlich Award, said, "The greatest contributors to my
project's success were my mentors." Working with Alfredo
Quinones-Hinojosa and a collaborator in Mexico, Oscar
Gonzalez-Perez, Chaichana teased apart the characteristics
of cells that give rise to brain tumors and found that most
of these cells share traits normally seen in neural stem
cells.

The 14 Young Investigators' Day Awards are named for
former Johns Hopkins students and well-respected former
faculty members. They are accompanied by a cash prize
funded by friends, family and the Johns Hopkins Medical and
Surgical Society. Some recipients say they feel a special
connection to their named award.

"Receiving the Hans J. Prochaska award is a great
honor since Dr. Prochaska received his MD and PhD degrees
here at Hopkins," said MD/PhD candidate Justin
Bailey. "His career is an inspiration for me as a
future scientist-clinician." Bailey, while working in the
lab of Robert Siliciano, discovered that rare
HIV-1-infected individuals known as elite suppressors
maintain undetectable virus levels and are indeed infected
with fully functional virus. They also discovered that this
so-called viral suppression is not controlled by
antibodies. "Understanding how elite suppressors keep their
viral levels so low may guide development of vaccines and
drugs," he said.

Working with Peter Esphenshade, Adam Hughes, a
PhD candidate in the Biochemistry,
Cellular and Molecular Biology program, discovered a
long-sought protein that controls cholesterol production
and potentially drug metabolism in humans. Recipient of the
David Israel Macht Award, Hughes said he wonders "if Dr.
Macht, who made major contributions to the field of
pharmacology, would take interest in our research if he
were here with us today. It's extremely humbling to receive
this honor as Dr. Macht was a tremendous scientist."

"Nupur Dinesh Thekdi was my floor mate when I first
joined Randy Reed's lab," said Cheuk Leung, also a
PhD candidate in the Biochemistry,
Cellular and Molecular Biology program. "It is my honor
to receive the award in memory of Nupur and his spirit for
science." Leung's project uncovered a stem cell-like role
for cells in the nose that repair severely damaged nerve
cells that contribute to our ability to smell.

Curtis Chong, an MD/PhD candidate in
pharmacology and molecular sciences, received the
Michael A. Shanoff Award for his project "Two Approaches to
Drug Discovery," through which he identified potential new
uses for three FDA-approved drugs.

"Fast, affordable and broad-reaching drug development
sharply contrasts with the current state of drug
discovery," said Chong, who spent a summer working in
Maputo, Mozambique, evaluating patients in an emergency
room. Many of the patients had drug-resistant malaria, and
Chong witnessed firsthand the fatal consequences of no
available treatments. "At the current cost and rate of drug
discovery, it will take more than 300 years for the number
of available drugs in the world to double — and it's
even worse in parts of the world where there is no
financial incentive," he said.

Upon his return to Johns Hopkins, Chong helped
establish the Johns Hopkins Clinical Compound Screening
Initiative, a collection of more than 2,000 existing drugs
that currently is being screened by many Johns Hopkins labs
for diseases from HIV to cancer.

Chong and colleagues found two drugs — an immune
suppressant and an antifungal — that block
cancer-induced blood vessel growth in mice. Separately they
have identified an antihistamine that shows promise for
halting multidrug-resistant malaria in mice. Because these
drugs already are FDA approved for other uses, "the path
from lab to clinical trails hopefully will be much shorter
than that of a newly derived drug," Chong said.

Grateful to his thesis advisers, Jun Liu and David
Sullivan, Chong said the best thing about being a Johns
Hopkins medical student "is working with such a talented
group of people who hold such high standards — it
motivates me to do my best each day."

Mette Strand Award winner Gabriela
Caraveo Piso, with adviser Stephen Desiderio, discovered a
new role — controlling calcium entry into cells
— for the TFII-I protein. Caraveo is a PhD candidate
in the immunology graduate program.Photo by Will Kirk / HIPS

Gabriela Caraveo Piso, a PhD candidate in the
immunology graduate program, received the
Mette Strand Award for her project "Action of TFII-I
Outside the Nucleus as an Inhibitor of Agonist Induced
Calcium Entry," where she discovered a new role —
controlling calcium entry into cells — for the
TFII-I, or TF "two-eye," protein previously known to
control genes.

In addition to delineating a previously unknown
mechanism by which calcium can enter cells, Caraveo's work
may have teased out the function of a protein implicated in
Williams-Beuren syndrome, a rare cognitive disorder
associated with overly social behavior and lack of spatial
awareness. Those affected are highly expressive, have
exceptionally strong language abilities and "can talk up a
storm," for example, but at the same time, they are poor at
global organization, having problems re-creating patterns
in drawings. The syndrome occurs in roughly one in 25,000
births and is caused by a deletion of a small section of
chromosome 7 that contains several genes, including the
gene that encodes the TFII-I protein. "We know that defects
in a cell's ability to take in calcium can lead to other
neurological and behavioral conditions," she said.

Caraveo, whose work was published last fall in
Science, attributes her success to her adviser,
Stephen Desiderio, who "profoundly shaped the way I
approach science by showing me how to channel enthusiasm
and passion into rigorous research design — he makes
science such a thrill," she said.

Steven Eliades, right, with his
adviser, Xiaoqin Wang. Eliades, an MD/PhD candidate in
biomedical engineering, is studying how the brain processes
many sound inputs. He received one of four Paul Erlich
Research Awards.Photo by Will Kirk / HIPS

Steven Eliades, an MD/PhD candidate in biomedical engineering,
received a Paul Erlich Research Award for his project
"Auditory-Vocal Interactions in the Primate Auditory
Cortex."

Eliades examined "how we listen to ourselves when we
talk" to figure out how the brain processes many sound
inputs. "We have to be able to hear everyone else despite
how loud our own voice is," Eliades said. "Otherwise, we
wouldn't be able to communicate." Likewise, being able to
hear ourselves as we talk allows the brain to correct any
speech errors, he explained.

By studying nerve cell activity in monkeys while they
vocalized, Eliades discovered two distinct groups of nerve
cells in the part of the brain responsible for processing
sound, the auditory cortex. One group of nerve cells was
turned off during vocalization, while the other group was
turned on, and both groups appeared to be controlled by
vocalization itself. By changing external sounds, Eliades
found that these two groups of nerve cells allow animals to
both hear outside sounds and monitor their own voices
during vocalization.

One major hurdle Eliades had to overcome was that
monkeys restrained in a lab refuse to "speak" reliably.
"For several years, this project seemed dead with failure
after failure," he said. Only after he figured out a way to
record free-roaming monkeys interacting with each other in
their colony did he begin to make some progress.

"This award means a lot to me personally and
professionally," said Eliades, adding that he is grateful
to his adviser, Xiaoqin Wang, "for giving me a huge amount
of freedom to come up with my own approach to the problem
and being patient enough to allow things to play out."